To better understand the interrelationships of insulin (IRI), glucagon (IRG) and somatostatin (IRSS) release from the normal and genetically diabetic islet of Langerhans: (1) normal and genetically diabetic Chinese hamster pancreases will be perfused in vitro to follow the onset and progression of abnormalities in hormone release starting at a young age; (2) hamster pancreases will be perfused in vitro with varying levels of Ca2 ion in the presence of glucose to determine the minimum level of Ca2 ion required for glucose-stimulated IRI release and the level of Ca2 ion which activates the K ion permeability channel and polarizes the diabetic beta cell (thus blocking IRI release); (3) young (pre) diabetic hamsters will be treated in vivo with an immunosuppressant to determine if an autoimmune reaction precipitates their diabetes; and (4) techniques for ob/ob mouse islet collagenase isolation and storage will be improved to be applied, eventually, to the perifusion of Chinese hamster islets for measurement of hormone release.